Candidate: Dr. Jennifer Slyker, PhD, is a Senior Fellow in the Division of Allergy and Infectious Diseases at the University of Washington. Dr. Slyker proposes a K01 Career Development Award to gain mentorship in epidemiology and clinical research which, combined with her rigorous background in immunology, will enable her to pursue a long-term career in molecular epidemiology focusing on women and children at risk for HIV. During the award period, Dr. Slyker will receive training in epidemiology, biostatistics, clinical trials, and CMV research by mentors with considerable expertise in these areas (Drs. John-Stewart, Richardson, Boeckh), all of whom are committed to provide intensive support and have extensive mentorship experience. The proposed research addresses a topic of high public health significance with important potential implications as CMV vaccines and treatments continue to evolve. The research plan will foster opportunities for Dr. Slyker to gain skills in complex analyses, study design and CMV pathogenesis. The candidate and research plan is anticipated to result in Dr. Slyker's development into an independent research scientist. The UW will provide an ideal milieu for Dr. Slyker's career development with access to resources and opportunities that will foster her long-term success. In addition, Dr. Slyker's continued collaboration with Kenyan pediatrician scientists will provide a context for the design of relevant future studies. Research: There is evidence that cytomegalovirus (CMV) infection contributes significantly to morbidity and mortality in HIV-1 infected infants. Several new advances offer hope for improved diagnosis, treatment and prevention of CMV in resource-limited settings. These include CMV diagnosis from dried blood spots, novel anti-CMV drugs with reduced toxicity, and progress toward the development of a CMV vaccine. For this K-application Dr. Slyker will conduct research using a repository of data and specimens from 3 Kenyan randomized controlled trials comprising HIV-infected women and their infants. CMV viral loads will be measured from stored specimens from the three trials. The aims of the study are 1) To determine the influence of breastfeeding on infant CMV acquisition. Time to CMV will be compared between infants randomized to breastfeeding versus formula feeding. 2) To evaluate the impact of maternal HAART on breast milk CMV viral load and vertical CMV transmission. Breast milk CMV viral loads will be compared at serial time-points during the first year post-partum between HIV-infected women randomized to ZDV/NVP versus HAART. 3) To evaluate the efficacy of maternal valacyclovir therapy during pregnancy and breastfeeding to reduce maternal CMV replication and CMV transmission. Time to CMV will be compared between infants born to HIV-infected women randomized to valacyclovir versus placebo. This complement of studies will provide important new data on the epidemiology of CMV in the setting of HIV-1 and will form a foundation for new interventions that may decrease infant morbidity and mortality. Public Health Relevance: Jennifer Slyker, PhD is a Senior Fellow in the Division of Allergy and Infectious Diseases at the University of Washington. For this K01 award, the career development plan and proposed research studies will pose analytical challenges and opportunities which will be combined with mentorship in epidemiology, statistical analyses, clinical trials design, and CMV virology which will enable the candidate to develop an independent research career in molecular epidemiology. The research findings will be central to the design of interventions to interrupt vertical cytomegalovirus transmission, a strategy aimed at reducing morbidity and mortality in HIV- infected infants.